Clinical trials of male hormonal contraception (MHC) use an androgen-progestin combination to suppress gonadotropins and spermatogenesis. Selective androgen receptor modulators (SARMs) that possess both androgenic and progestational activity are an attractive approach to MHC and are being developed by NICHD. I participated in recent NICHD supported Phase 1 studies on the oral SARMs, 11?-methyl-nortestosterone dodecylcarbonate (11?-MNTDC) and dimethandrolone undecanoate (DMAU). While analyzing data from these studies, I noticed weight gain and significant changes in HDL, similar to changes that occurred in MHC trials of men receiving testosterone-progestin combinations. Our long-term objective is to develop a novel SARM with specific characteristics to maximize beneficial and minimize adverse effects on metabolic parameters. The premise of this study is to comprehensively assess metabolic effects of SARMs and androgen-progestin combinations in order to guide selection choice of which compound(s) is most beneficial to long-term health. The study aims are: AIM 1: Compare the impact of SARMs and testosterone-progestin combinations on weight, insulin resistance, and lipids in healthy men. This will be assessed retrospectively using residual sera from prior trials. We hypothesize that certain progestins will contribute to insulin resistance and dyslipidemia compared to androgens alone. AIM 2: Prospectively compare the effects of DMAU with and without oral levonorgestrel (an androgenic progestin) on body composition and metabolic parameters. In an ongoing 12-week placebo- controlled study, as a corollary to the main study we will compare the impact of DMAU alone or with levonorgestrel (LNG) on changes in lean mass. We hypothesize that DMAU will increase lean and decrease fat mass. Addition of LNG, an androgenic progestin, to DMAU could decrease lean mass and increase insulin resistance and dyslipidemia compared to DMAU alone. This clinical study will directly provide training on and experience with: 1) hands-on laboratory-based research experience using immunoassays and liquid chromatography/tandem mass spectrometry; 2) measurement of body composition using bioelectrical impedance and DXA scanning; 3) clinical research training including regulatory approval processes, data management, IND amendments, and grant writing; and 4) power calculations and statistical analysis of data across multiple trials. This study will produce preliminary data to support a planned K23 application to NICHD. Collectively, this study and my proposed training plan will significantly advance my career in translational research and assist in my goal of becoming an independent investigator in male contraception with a focus on metabolic effects.